Steroids with C-11 functionality are crucial for biological activity and are observed in a number of drug molecules including steroid hormones. Steroids with C-11 functionality are well-known for biological activity and are obtained in a number of naturally occurring molecules such as cortisone, hydrocortisone, and corticosterone. Potent synthetic corticosteroids such as dexamethasone, triamcinolone, and fluticasone also possess C-11 hydroxy functionality. Stereoselective C-11 functionalization in the steroids is one of the challenging targets for synthetic organic chemists because it involves severe steric interactions due to C-18 and C-19 angular methyl groups. Introduction of the C-11 R-hydroxyl functionality via microbial hydroxylation by the Syntex et al. in J. Am. Chem. Soc, 1952, 74, 5933-5936 and via long-range chemical functionalization by Breslow et al. in Acc. Chem. Res, 1980, 13, 170-177 is well documented.
PCT application no. 2002014342A1 discloses a series of novel steroid derivatives wherein the steroid derivatives are antibacterial agents. The steroid derivatives also act to sensitize bacteria to other antibiotics including erythromycin and novobiocin. The invention features compounds of the formula I
wherein:
fused rings A, B, C, and D are independently saturated or fully or partially unsaturated; and R1 through R4, R6, R7, R11, R12, R15, R16, and R17 is each independently selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, a substituted or unsubstituted (C1-C10) aminoalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted arylamino-(C1-C10) alkyl, (C1-C10) haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, oxo, a linking group attached to a second steroid, a substituted or unsubstituted (C1-C10) aminoalkyloxy, a substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkylcarboxy, a substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, a substituted or unsubstituted (C1-C10) aminoalkylcarboxamido, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, P.G.-HN—HC(Q5)-C(O)—O—, (C1-C10) guanidinoalkyloxy, (C1-C10) quaternaryammonium-alkylcarboxy, and (C1-C10) guanidinoalkylcarboxy, where Q5 is a side chain of any amino acid, P.G. is an amino protecting group.
Article titled “An efficient method for the synthesis of methyl 11α-amino-3α,7α-diacetoxy-12-oxo-5b-cholan-24-oate” by D B Salunke et al. published in Tetrahedron, Volume 61, Issue 14, 4 Apr. 2005, Pages 3605-3612 reports the synthesis of methyl 11α-azido-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate, methyl 11β-azido-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate and methyl 11α-amino-3α,7α-diacetoxy-12-oxo-5β-cholan-24-oate. The assignment of the stereochemistry at C-11 of compound 13 was supported by the 1H NMR spectrum in which the C-11 proton appeared as a doublet (d 4.06 ppm, JZ10.8 Hz) due to trans diaxial coupling between the C-11 and C-9 protons.

Article titled “Amino functionalized novel cholic acid derivatives induce HIV-1 replication and syncytia formation in T cells” by D B Salunke et al. published in J Med Chem., 2006 Apr. 20; 49(8), 2652-2655 reports synthesis of C-11 azido/amino functionalized cholic acid derivatives in excellent yields. Contrary to the previous prediction of analogous compounds to be HIV-1 protease inhibitors, in the present study these novel cholic acid derivatives induced host cell fusion during the progress of HIV-1 infection and produced multinucleated giant cells.

Article titled “Synthesis of novel steroidal inhibitors of HIV-1 protease” by Marples et al. published in Tetrahedron, Volume 54, Issue 39, 24 Sep. 1998, Pages 11907-11924 reports the design and synthesis of potential steroidal HIV-1 protease inhibitors is described. Compounds derived from 11-amino-12-keto-cholanic acid derivatives show modest activity.

Article titled “Synthesis of bile acid dimers linked with 1,2,3-triazole ring at C-3, C-11, and C-24 Positions” by N G Aher et al. published in Synlett, 2005, 14, pp 2155-2158 reports 1,3-dipolar cycloaddition of propargyl ester of a bile acid to an azide group attached at different positions of another bile acid gave three new 1,2,3-triazole-containing dimeric analogues in excellent yields.
Therefore, there is need in the art to develop C-11 functionalized bile acid derivatives which are easily prepared and used for pharmaceutical purpose. Accordingly, the present invention describes the C-11 functionalized bile acid derivatives which show anticancer and antimicrobial activity.